Nanotechnology holds great promise for cancer therapy, but difficult chemistry problems have impeded progress in efficacy, elimination of side effects, and commercial production. These problems are not a factor with the engineered plant virus nanoparticle that will be used in the proposed research. Through millions of years of evolution, this unique virus has solved production, uniformity, biologic, and pharmacokinetic problems. This plant virus is in the human food chain, is non toxic, and is of low immunogenicity. It can load medical imaging agents and/or therapeutic drugs into its "cargo chamber" by a simple process. The virus can not only be engineered to identify and enter cancer cells but can target and release drug payloads inside cell structures, such as the nucleus where most chemotherapy drugs operate, bypassing most cancer cell defenses. In this project, we will implement a new approach to increase production of these plant virus nanoparticles. We will also demonstrate effective delivery of imaging agents and chemotherapy drugs to drug resistant cancer cells and to tumors in an animal model, in preparation for a possible Phase II research project leading to further development of the best drug formulation and an IND application for clinical trials.